ArticlePloS one2021
Spatial protein heterogeneity analysis in frozen tissues to evaluate tumor heterogeneity.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Gut plasma membrane proteomes reflect the distinct feeding strategies of Nezara viridula and Diaphorina citri.Scientific reports · 2026Article
- Gut plasma membrane proteomes of adults and larvae of the European honey bee, Apis mellifera.Scientific reports · 2025Article
- Single-cell western blotting of cytoplasmic cytokeratin 8 proteoforms.The Analyst · 2025Article
- Single-cell western blotting of cytoplasmic cytokeratin 8 proteoforms.bioRxiv : the preprint server for biology · 2025Article
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5 authors.
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Abstract
A new workflow for protein-based tumor heterogeneity probing in tissues is here presented. Tumor heterogeneity is believed to be key for therapy failure and differences in prognosis in cancer patients. Comprehending tumor heterogeneity, especially at the protein level, is critical for tracking tumor evolution, and showing the presence of different phenotypical variants and their location with respect to tissue architecture. Although a variety of techniques is available for quantifying protein expression, the heterogeneity observed in the tissue is rarely addressed. The proposed method is validated in breast cancer fresh-frozen tissues derived from five patients. Protein expression is quantified on the tissue regions of interest (ROI) with a resolution of up to 100 μm in diameter. High heterogeneity values across the analyzed patients in proteins such as cytokeratin 7, β-actin and epidermal growth factor receptor (EGFR) using a Shannon entropy analysis are observed. Additionally, ROIs are clustered according to their expression levels, showing their location in the tissue section, and highlighting that similar phenotypical variants are not always located in neighboring regions. Interestingly, a patient with a phenotype related to increased aggressiveness of the tumor presents a unique protein expression pattern. In summary, a workflow for the localized extraction and protein analysis of regions of interest from frozen tissues, enabling the evaluation of tumor heterogeneity at the protein level is presented.
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